Medicinal composition for treatment of chronic hepatitis c

a technology for chronic hepatitis c and composition, which is applied in the direction of drug compositions, antibody medical ingredients, peptide/protein ingredients, etc., can solve the problems of not being able to clarify whether hcv invades a cell or only adheres to its surface, and the infection of chronic hcv becomes a serious problem, so as to prevent side effects of hepatic cirrhosis and enhance immune function

Inactive Publication Date: 2007-05-17
INTPROP CONSULTING +1
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Benefits of technology

[0014] An object of the present invention is to provide a method and a pharmaceutical composition, for augmenting a function of an immune system, treating chronic hepatitis C and preventing sideration of hepatic cirrhosis and hepatic cell carcinoma, in chronic HCV-infected patients, by clarifying a mechanism of HCV persistent infection, particularly, a mechanism of MICA / B expression induced by IFNa in dendritic cells.

Problems solved by technology

The number of patients suffering from HCV positive hepatic cell carcinoma is increasing on a global basis, and chronic HCV infection is becoming a serious problem.
This therapeutic method remarkably improved the probability of HCV eradication as compared with a therapy using singly IFN-a, however, half or more of patients are not cured by this combination therapy.
However, this method cannot clarify whether HCV invades a cell or only adheres to its surface.

Method used

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  • Medicinal composition for treatment of chronic hepatitis c
  • Medicinal composition for treatment of chronic hepatitis c
  • Medicinal composition for treatment of chronic hepatitis c

Examples

Experimental program
Comparison scheme
Effect test

example 1-1

Induction of MICA / B Expression by Cytokine

[0073] Whether MICA / B is induced by various cytokines or not was investigated in DCs derived from healthy donors and HCV-infected patients having or not having ALT abnormality. Monocyte-derived DCs from healthy donors (N-DC) and HCV-infected patients (HCV-DC) were prepared, and at day 6 of culturing, stimulated for 24 hours with IFNa (1000 U / mL), IFNβ (1000 U / mL), TNFa (10 ng / mL), IL-12 (10 ng / mL), IL-15 (50 ng / mL) and IL-18 (20 ng / mL). Then, MICA / B expression was analyzed by flow cytometry. The results are shown in FIG. 1.

[0074] DCs from normal donors (N-DC) responded to IFNa or IFNβ to express MICA / B, however, DCs from HCV-infected patients (HCV-DC) did not express MICA / B in any cases. IL-15 could apparently induce MICA / B, in N-DC and HCV-DC. In contrast, TNFa, IL-12 or IL-18 did not induce MICA / B expression.

example 1-2

RT-PCR Analysis of MICA / B mRNA

[0075] Total RNAs were isolated from DCs not stimulated, DCs stimulated with IL-15 (50 ng / mL) and DCs stimulated with IFNa (1000 U / mL), respectively, and expression of MICA mRNA and expression of MICB mRNA were analyzed by RT-PCR. Consequently, results corresponding to the above-mentioned results of flow cytometry were obtained.

example 1-3

Difference of MICA / B Expression Depending on Presence or Absence of ALT Abnormality

[0076] MICA / B expression was compared among healthy donors (n=15)(HV), chronic HCV-infected patients showing abnormal ALT (n=10)(CH-1) and chronic HCV-infected patients having persistent normal ALT level (n=10)(CH-2). MICA / B expression of DCs stimulated with IFNa or IL-15 was checked by flow cytometry, and represented as percent of positive cells. The results are shown in FIG. 2. In the drawing, a horizontal bar represents an average, a vertical bar represents SD, and * represents p<0.01. HCV-DC, when stimulated with IFNa, did not express MICA / B irrespective of the condition of ALT abnormality. This suggests that no MICA / B expression in response to IFNa or IFNβ in HCV-DC is not caused by chronic inflammation of liver.

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Abstract

The present invention provides a pharmaceutical composition for treating chronic hepatitis C characterized by comprising at least one active ingredient selected from the group consisting of IL-15, myeloid dendritic cell maturation stimulators (for example, CpG oligo deoxynucleotide, GM-CSF, IL-4, LPS, CD40L, polyI:C, TNF-a and IFN-?) and lectin-binding substances (for example, mannose carbohydrate, fucose carbohydrate and anti-lectin antibody); and a method of treating chronic hepatitis C by using such active ingredient(s). In the above pharmaceutical composition and therapeutic method, it is possible to use INF-a together with these active ingredients.

Description

TECHNICAL FIELD[0001] The present invention relates to a method and a pharmaceutical composition for treating chronic hepatitis C. BACKGROUND ART [0002] A hepatitis C virus (HCV) is a single stranded plus sense RNA virus belonging to the Flavivirus family, and causes persistent infection in 70% or more of infected patients. A most important feature of HCV persistent infection is a possibility of progress of hepatic diseases from mild hepatitis to hepatic cirrhosis and hepatic cell carcinoma. The number of patients suffering from HCV positive hepatic cell carcinoma is increasing on a global basis, and chronic HCV infection is becoming a serious problem. [0003] For preventing progress of hepatic diseases and subsequent onset of hepatic cell carcinoma, it is necessary to eradicate HCV from a HCV-infected patient. For this purpose, a therapy combining IFN-a and ribavirin is currently used as a standard therapeutic method for chronic HCV infection (Japanese Patent Application Laid-Open (...

Claims

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Application Information

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Patent Type & Authority Applications(United States)
IPC IPC(8): A61K38/20A61K31/716A61K31/715A61K39/395A61K31/7004A61K31/7088A61K38/18A61K38/19A61K38/21A61P1/16A61P31/14
CPCA61K31/7004A61K31/7088A61K38/191A61K38/193A61K38/2026A61K38/2086A61K38/212A61K38/217C07K16/244C07K16/2833C07K16/2851C07K16/2866C07K2317/76A61K2300/00A61P1/16A61P31/14A61P35/00A61P43/00
Inventor HAYASHI, NORIO
Owner INTPROP CONSULTING
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